Melanotan II (MT2)

Melanotan 2 Peptide

Melanotan II (MT-II) is a synthetic, cyclic heptapeptide. It is an analog of the natural alpha-melanocyte-stimulating hormone (alpha-MSH). This synthesized peptide displays altered receptor affinity compared to the endogenous hormone, allowing it to interact with several melanocortin receptor (MCR) subtypes. While its primary initial research focused on stimulating melanogenesis (the production of melanin) within skin cells, MT-II has also been observed to interact with receptors linked to appetite control, sexual function, and various arousal-related pathways.

Melanotan 2 Peptide Overview

Melanotan II (MT-II) is a synthetic alpha-MSH analogue. Its development began at the University of Arizona in the 1980s, originating from research that explored alpha-MSH's effects on pigmentation and broader physiological responses. Early studies observed that alpha-MSH induced both skin darkening and specific behavioral effects in animal models, leading to further investigation into its analogs.

Originally conceived as a potential agent for promoting skin pigmentation without the need for ultraviolet exposure, MT-II was later found to exhibit a broader range of biological activities. Research has since focused on its influence on sexual behavior, appetite regulation, and metabolic processes. Preliminary findings have suggested roles in modulating compulsive or addictive tendencies, suppressing appetite, and regulating glucagon, though these effects remain subjects of investigation and are not established for clinical application.

Melanotan 2 Peptide Structure

MT-II is a synthetic cyclic heptapeptide, meaning it is composed of seven amino acids arranged in a ring structure. This cyclic configuration enhances its stability and contributes to its specific binding profile as a potent agonist for the melanocortin receptor family. The precise structure is key to its wide range of pharmacological activity.

Melanotan 2 Peptide Research

Melanotan II and Melanocortin Signaling

Melanotan II (MT-II) exerts its biological activity through interactions with the melanocortin receptor (MCR) family. This receptor group has five distinct subtypes (MC1R–MC5R), each linked to specific physiological functions. MT-II demonstrates the highest affinity for MC4R and MC1R, with moderate or weak binding observed at MC3R. This diversity of receptor distribution across the body explains the peptide’s broad systemic effects.

MCR Subtype

Primary Tissue Location

Associated Physiological Function

MC1R

Melanocytes

Stimulates melanin synthesis, leading to skin and hair pigmentation.

MC2R

Adrenal Cortex

Mediates glucocorticoid (e.g., cortisol) release and stress response.

MC3R

Central Nervous System

Implicated in appetite control and metabolic homeostasis.

MC4R

Central Nervous System

Influences feeding behavior, sexual function, arousal, and energy expenditure.

MC5R

Sweat Glands, Pancreas

Thought to be involved in exocrine secretion and metabolic regulation.

Melanotan II and Autism

Recent investigations into Melanotan II (MT-II) have revealed promising findings regarding its potential influence on Autism Spectrum Disorder (ASD). Experimental evidence from a maternal immune activation (MIA) mouse model of ASD suggests that MT-II administration may alleviate certain autistic-like traits. Studies highlight the therapeutic role of oxytocin in improving social and behavioral deficits associated with the condition.

By using the MIA mouse model, which reliably reproduces core ASD features, researchers examined whether MT-II—known to enhance oxytocin secretion—could modulate behavioral impairments. Their findings demonstrated that MT-II treatment reversed several hallmark symptoms, including reduced communication, impaired social interaction, and repetitive behavioral patterns.

Furthermore, the study observed that MT-II significantly upregulated oxytocin receptor expression in specific brain regions associated with social cognition. This suggests a mechanistic link between MT-II–induced oxytocin signaling and the mitigation of ASD-related behaviors. Collectively, these results point toward the potential utility of MT-II as a modulator of neuroendocrine pathways involved in social behavior and developmental neurodisorders.

These results not only highlight potential strategies for creating ASD treatments but also help identify a specific neural pathway that may play a central role in the disorder’s development, supporting the advancement of both therapeutic and preventive approaches.

Melanotan 2 and Hunger

Substantial evidence indicates that MT-II can reduce fat accumulation and suppress hunger in animal studies. Researchers have identified that the melanocortin-4 receptor (MC4R) is involved in regulating food preference and intake, with MT-II acting as a strong activator of this receptor. When administered to mice, MT-II not only decreases overall food consumption but also alters their preference for high-fat foods. Treated mice tend to avoid fatty foods they would normally favor, while mice lacking the MC4R receptor show no such changes and remain unaffected by MT-II.

The activity of MT-II resembles that of leptin, a hormone that signals satiety by reducing appetite and cravings. However, leptin has proven ineffective in treating obesity, likely due to the existence of two distinct satiety pathways—one dependent on leptin and one independent of it. Studies suggest that MT-II effectively stimulates both pathways, making it a potentially superior external agent for appetite suppression. Further research has revealed that MT-II also influences the expression of thyrotropin-releasing hormone (TRH), a gene linked to the leptin-related satiety pathway and MC4R activation.

Melanotan 2 and Diabetes

The development of diabetes is characterized by elevated blood glucose levels, excessive glucagon secretion, and increased production of ketone bodies. It is recognized that leptin helps counter these conditions by enhancing glucose uptake, reducing glucagon release, and disrupting the pathways responsible for ketone formation—effects that occur independently of insulin.

Studies have shown that leptin’s regulation of blood sugar is mediated by melanocortin receptors, with MT-II demonstrating comparable effects. This similarity is noteworthy because, unlike leptin, MT-II can more easily cross the blood-brain barrier. As a result, externally administered leptin often fails to reach the central nervous system in sufficient amounts to be effective, whereas MT-II’s greater accessibility gives it a pharmacological advantage despite both peptides acting through nearly identical melanocortin pathways.

Melanotan 2, Impulse Control, and Alcohol Intake

Building on evidence that MT-II influences oxytocin signaling and associated behaviors seen in ASD, research has also identified a potential role of the MC4R receptor in regulating impulse control. Experimental studies in rats have shown that MT-II administration decreases alcohol consumption while increasing water intake, even in animals with a preference for alcohol. Furthermore, newer research indicates that MT-II acts synergistically with naltrexone, enhancing its effectiveness more than sevenfold in reducing binge-like ethanol intake in mice.

These results indicate that MT-II could serve not only as a potential therapy for alcohol-related disorders but also as a key to understanding deeper neural mechanisms of craving and desire in the brain. This line of research could broaden insight into how oxytocin influences impulsivity, appetite, and addiction.

Melanotan 2 and Erectile Dysfunction

Erectile dysfunction (ED) is typically linked to vascular complications and commonly treated with medications such as sildenafil (Viagra), which enhance blood circulation. However, since not all ED cases stem from vascular issues, these drugs can be ineffective for certain men and most women with low sexual desire. MT-II has been shown to be an effective therapy for ED, with evidence suggesting its broader potential due to its activity within the central nervous system rather than solely on vascular pathways. In clinical studies, approximately 80% of men unresponsive to Viagra experienced improvement with MT-II treatment. Furthermore, MT-II continues to be explored as a therapeutic option for both male and female sexual desire disorders.

Article Author

This literature review was written, compiled, and organized by Dr. Mac E. Hadley, Ph.D., a distinguished authority in melanocortin peptide research and pharmacology. Dr. Hadley is renowned for discovering that melanocortin peptides influence sexual function in both men and women—a breakthrough that spurred clinical interest in Melanotan II. His pioneering work at the University of Arizona greatly advanced scientific understanding of melanocortin receptor biology, peptide analog synthesis, and their therapeutic roles in neuroendocrine and metabolic regulation.

Scientific Journal Author

Dr. Mac E. Hadley worked closely with leading researchers including Dr. Victor J. Hruby, Dr. H. Wessells, and Dr. Stephen H. King, whose collaborative studies deepened knowledge of Melanotan II pharmacology. Their publications in major journals such as Peptides, Life Sciences, and the International Journal of Impotence Research clarified receptor selectivity, molecular function, and the clinical relevance of melanocortin receptor agonists. Collectively, their research has formed the scientific foundation for understanding Melanotan II’s diverse effects on pigmentation, energy balance, neural protection, and sexual health.

Reference Citations

• Ryakhovsky, Vladimir V et al. "The first preparative solution phase synthesis of Melanotan II." Beilstein Journal of Organic Chemistry vol. 4 (2008): 39. doi:10.3762/bjoc.4.39. https://pubmed.ncbi.nlm.nih.gov/19043625/
• Hadley, Mac E. "Discovery that a melanocortin regulates sexual functions in male and female humans." Peptides, Volume 26, Issue 10, 2005, Pages 1687-1689. https://doi.org/10.1016/j.peptides.2005.01.023
• King, Stephen H et al. "Melanocortin receptors, melanotropic peptides and penile erection." Current topics in medicinal chemistry vol. 7,11 (2007): 1098-1106. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2694735/
• Peters, Björn, et al. "Melanotan II: a possible cause of renal infarction: review of the literature and case report." CEN case reports vol. 9,2 (2020): 159-161. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7148395/
• Ter Laak, Mariël P, et al. "The potent melanocortin receptor agonist melanotan-Il promotes peripheral nerve regeneration and has neuroprotective properties in the rat." European Journal of Pharmacology vol. 462,1-3 (2003): 179-83. https://pubmed.ncbi.nlm.nih.gov/12591111/
• Wessells, H et al. "Melanocortin receptor agonists, penile erection, and sexual motivation: human studies with Melanotan II." International journal of impotence research vol. 12 Suppl 4 (2000): S74-9. https://pubmed.ncbi.nlm.nih.gov/11035391/
• Minakova E, Lang J, Medel-Matus JS, Gould GG, Reynolds A, Shin D, Mazarati A, Sankar R. "Melanotan-Il reverses autistic features in a maternal immune activation mouse model of autism." PLoS One. 2019 Jan 10;14(1):e0210389. doi: 10.1371/journal.pone.0210389. https://pubmed.ncbi.nlm.nih.gov/30629642/
• Dorr RT, Lines R, Levine N, Brooks C, Xiang L, Hruby VJ, Hadley ME. "Evaluation of melanotan-II, a superpotent cyclic melanotropic peptide in a pilot phase-I clinical study." Life Sci. 1996;58(20):1777-84. https://pubmed.ncbi.nlm.nih.gov/8637402/

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Storage

Storage Instructions

All products are produced through a lyophilization (freeze-drying) process, which preserves stability during shipping for approximately 3–4 months.

• Lyophilized Peptides (Powder): The stable, white crystalline structure is safe for storage at room temperature for several weeks. For short-term use (within a few days, weeks, or months), refrigeration below 4 degrees C (39 degrees F) is sufficient. For extended storage (lasting several months to years), it is recommended to keep peptides in a freezer at -80 degrees C (-112 degrees F) to maintain the peptide’s structural integrity and ensure long-term stability.
• Reconstituted Peptides (Solution): After reconstitution with bacteriostatic water, peptides must be stored in a refrigerator (below 4 degrees C). Once mixed, they typically remain stable for up to 30 days.

Best Practices For Storing Peptides

Proper storage of peptides is critical to maintaining the accuracy and reliability of laboratory results. Following correct procedures helps prevent contamination, oxidation, and degradation, ensuring that peptides remain stable and effective for extended periods.

Storage Duration

Peptide Form

Recommended Temperature

Key Practice

Short-Term

Lyophilized or Reconstituted

Below 4 degrees C (Refrigerated)

Keep cool and shielded from light.

Long-Term

Lyophilized

-80 degrees C (Frozen)

Minimize freeze-thaw cycles; avoid frost-free freezers.

Solution (Max 30 days)

Reconstituted

Below 4 degrees C (Refrigerated)

Use sterile buffers; store in aliquots.

Preventing Oxidation and Moisture Contamination

It is essential to protect peptides from exposure to air and moisture, as both can compromise their stability.

• Moisture Contamination: To avoid condensation forming on the cold peptide or inside its container, always allow the vial to reach room temperature before opening after removal from the freezer.
• Air Exposure: The peptide container should remain closed as much as possible. After removing the required amount, promptly reseal it. Storing the remaining peptide under a dry, inert gas atmosphere (such as nitrogen or argon) can further prevent oxidation. Peptides containing cysteine (C), methionine (M), or tryptophan (W) residues are especially sensitive to air oxidation and require extra care.
• Freeze-Thaw Cycles: To preserve long-term stability, avoid frequent thawing and refreezing. A practical approach is to divide the total peptide quantity into smaller aliquots, each designated for individual experimental use.

Storing Peptides In Solution

Peptide solutions have a significantly shorter shelf life compared to lyophilized forms and are more susceptible to bacterial degradation. Peptides containing cysteine, methionine, tryptophan, aspartic acid, glutamine, or N-terminal glutamic acid residues tend to degrade more rapidly when stored in solution.

• Best Practice: If storage in solution is unavoidable, it is recommended to use sterile buffers with a pH between 5 and 6. The solution should be divided into aliquots to minimize freeze-thaw cycles.
• Stability: Under refrigerated conditions at 4 degrees C, most peptide solutions remain stable for up to 30 days. However, peptides known to be less stable should be kept frozen when not in immediate use.

Peptide Storage Containers

Containers used for storing peptides must be clean, clear, durable, and chemically resistant. They should also be appropriately sized to match the quantity of peptide being stored, minimizing excess air space.

• Vial Types: Both glass and plastic vials are suitable. High-quality glass vials provide the best overall characteristics (clarity, stability, and chemical inertness). Plastic varieties (polystyrene or polypropylene) are often used for shipping.
• Transfer: Peptides can be safely transferred between glass and plastic vials to suit specific storage or handling requirements.

Peptide Storage Guidelines: General Tips

When storing peptides, follow these best practices to maintain stability and prevent degradation:

• Store peptides in a cold, dry, and dark environment.
• Avoid repeated freeze-thaw cycles.
• Minimize exposure to air to reduce the risk of oxidation.
• Protect peptides from light.
• Do not store peptides in solution long term; keep them lyophilized whenever possible.
• Divide peptides into aliquots based on experimental needs.